Cost-effectiveness of zoledronic acid plus endocrine therapy in premenopausal women with early stage breast cancer based on results of the ABCSG-12 study.

Abstract

Abstract Abstract #2112 Background: Zoledronic acid (ZOL) has demonstrated antitumor and antimetastatic activity in preclinical and early clinical studies. The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of ovarian suppression using goserelin combined with 3 years of endocrine therapy (ET) with anastrozole (ANA) or tamoxifen (TAM) with or without ZOL (4 mg q6m) in 1803 premenopausal women with endocrine-responsive early breast cancer. After a median follow-up of 47.8 months, there was no significant difference (p>0.05) between patients who received TAM vs. ANA in disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS). However, the addition of ZOL to ET significantly reduced the risk of DFS events by 36% (HR = 0.64, p = 0.011) and RFS by 35% (HR=0.65, p=0.014) compared with ET alone. There was a nonsignificant trend in OS favoring ZOL (p= 0.101). ZOL was generally well tolerated, and there were no confirmed cases of ONJ or renal toxicity.
 Methods: A Markov model was used to generate preliminary estimates the cost-effectiveness (cost per quality adjusted life year [QALY] gained) of 3 years of ZOL+ET compared to 3 years of ET alone, in premenopausal women with early stage breast cancer. A lifetime timeframe was employed. Probabilities of recurrence with ZOL+ET and ET alone were based on the results of ABCSG-12 trial (ASCO 2008; #LBA4). Outcomes after recurrence were based on published studies and assumed to be the same for ZOL+ET and ZOL only. A US healthcare system perspective was employed. Costs of study medications were based on wholesale acquisition costs. Costs of ZOL administration were based on Medicare fees. Costs of breast cancer care were based on published sources. Costs and QALYs were discounted at 3% annually. Results were generated under 2 scenarios regarding duration of benefit (reduction in risk of recurrence) with ZOL: (1) benefits persist until death (“lifetime benefit scenario”): (2) benefits persist to the maximum follow-up reported for ABCSG-12 (84 months) (“trial benefit scenario”).
 Results: The additional cost of 3 years of ZOL 4 mg q6m is approximately $5,000 (including drug administration costs). Under the lifetime benefit scenario, the additional costs of ZOL are more than offset by savings in costs of recurrences, and ZOL+ET is the “dominant strategy”, reducing total costs while increasing QALYs. Under the trial benefit scenario, the additional costs of ZOL are partially offset by savings in the costs of recurrences. However, the cost effectiveness of ZOL+ET vs. ET only is highly favorable (i.e., <$10,000 per QALY gained).
 Conclusion: In premenopausal women with early stage breast cancer, adding zoledronic acid to adjuvant endocrine therapy is likely to be cost-effective use of healthcare resources from a US healthcare system perspective. Further analyses are ongoing to refine these estimates and examine sensitivity of model results to key assumptions and parameter estimates. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2112.